CNS & pituitary tumors

• CNS embryonal tumor, not elsewhere classified (NEC) / not otherwise specified (NOS) is a type of central nervous system (CNS) tumor with embryonal characteristics that does not fit into a specific molecularly defined category of CNS embryonal tumor

• Embryonal tumor originating in the CNS
• It is classified as NEC if the identified molecular features do not match an existing CNS WHO entity and NOS if there is insufficient tissue for further analysis or if molecular testing cannot be performed for other reasons

• Unknown at this time; may vary depending on the specific underlying genetic alterations

• Clinical presentation is nonspecific and depends on the location of the tumor

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Contributed by Thomas Pearce, M.D., Ph.D. and Ian Lagerstrom, M.D.

• Primitive / embryonal appearing tumor cells but no distinctive features that allow discriminating embryonal tumor NOS / NEC from a molecularly defined category
• Evaluation of cerebrospinal fluid for microscopic tumor cells is important for staging

The above tumor is found in the brain. Next generation sequencing was performed and a PLAG2 amplification was detected. It consists of tightly packed cells with minimal cytoplasm and a high mitotic rate. GFAP is negative and synaptophysin is variably positive. What is the diagnosis?

1. Embryonal tumor, not elsewhere classified (NEC)
2. Embryonal tumor with multilayered rosettes
3. Ependymoma
4. Medulloblastoma

A. Embryonal tumor, not elsewhere classified (NEC). Embryonal tumor, NEC is a poorly differentiated tumor consisting of tightly packed cells with minimal cytoplasm and a high mitotic rate that are GFAP negative and variably positive for synaptophysin. The diagnosis of CNS embryonal tumor, NEC requires the exclusion of other CNS embryonal tumors with recurrent molecular alterations. PLAG2 amplification is not currently a molecularly defining mutation for this group of tumors.

Answer B is incorrect because embryonal tumor with multilayered rosettes is characterized by altered C19MC (in ~90% of cases) and overexpression of LIN28A protein. Answer C is incorrect because the absence of GFAP expression and the molecular finding is not consistent with ependymoma. High grade ependymomas can have an embryonal type appearance and high mitotic rate, so it is important to include in the differential diagnosis. Answer D is incorrect because medulloblastomas have different defining molecular alterations, although they are typically at least focally positive for synaptophysin.

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Reference: CNS embryonal tumor, NOS / NEC

A small biopsy from a large supratentorial brain mass is taken from a 2 year old girl. The biopsy shows a densely cellular tumor with embryonal cytologic features and vague multilayered rosette-like architecture. The tumor is immunoreactive for synaptophysin and negative for GFAP. Tissue is sent for additional molecular studies; however, the molecular testing failed due to insufficient nucleic acids. How should this tumor be classified?

1. Embryonal tumor, not elsewhere classified (NEC)
2. Embryonal tumor, not otherwise specified (NOS)
3. Embryonal tumor with multilayered rosettes, C19MC altered
4. High grade astrocytoma, NOS

B. Embryonal tumor, not otherwise specified (NOS). Embryonal tumor, NOS displays embryonal morphology and immunophenotype but molecular testing needed for a more specific diagnosis cannot be performed. Answer C is incorrect because embryonal tumor with multilayered rosettes is characterized by alterations of the chromosome 19 microRNA cluster (C19MC) and molecular confirmation of this finding is needed. Answer A is incorrect because embryonal tumor, NEC requires molecular testing to be performed and no molecular alterations that would allow for a diagnosis of a more specific molecularly defined CNS embryonal tumor entity to be identified. Answer D is incorrect because the tumor has embryonal rather than glial morphology and immunophenotype.

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Reference: CNS embryonal tumor, NOS / NEC